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We have conducted a thorough review of the literature to assess the evidence for supporting a cause-and-effect linkage between scalp condition and resultant hair condition. Over 20 epidemiological studies have been published covering a wide range of abnormal scalp conditions in which consequent impacts to the hair have been documented. A treatment study was conducted to demonstrate not only that impaired scalp condition led to impaired hair quality but that the impacts to hair are reversible upon normalization of the scalp condition. A proposed explanation involves the impact of scalp oxidative stress, which is part of the etiology of these scalp conditions as well as normal aging, in interfering with the normal keratinization of the pre-emergent hair cuticle. This perturbed cuticle impedes normal fiber anchorage and emerges more brittle and fragile than normal cuticle leading to accelerated physical degradation, mirroring the effects of chronological aging of the hair fiber. The consequences of the rapid cuticle degradation result in hair that is more vulnerable to mechanical insults and compromised overall quality.Nous avons mené un examen approfondi de la littérature médicale pour évaluer les preuves étayant un lien de cause à effet entre l’état du cuir chevelu et celui des cheveux. Plus de 20 études épidémiologiques ont été publiées, couvrant un large éventail d’affections du cuir chevelu pour lesquelles des impacts conséquents sur les cheveux ont été documentés. Une étude de traitement a été menée pour démontrer non seulement qu’une altération du cuir chevelu entraînait une altération de la qualité des cheveux, mais aussi que les impacts sur les cheveux étaient réversibles après normalisation de l’état du cuir chevelu. Une explication proposée inclut l’impact du stress oxydatif sur le cuir chevelu, qui fait partie de l’étiologie de ces affections du cuir chevelu ainsi que du vieillissement normal, en interférant avec la kératinisation normale de la cuticule du cheveu à son point d’émergence. Cette cuticule perturbée gêne l’ancrage normal des fibres et fait émerger des cuticules plus fragiles et friables que la normale, entraînant une dégradation physique accélérée, reflet des effets du vieillissement chronologique des fibres capillaires. La dégradation rapide de la cuticule rend les cheveux plus vulnérables aux agressions mécaniques et compromet leur qualité globale.

OBJECTIVE Increasing scalp hair fullness is a global unmet consumer need. An approach to decrease hair shedding by reducing scalp stratum corneum oxidation via a combination of antioxidant and barrier-enhancing technologies has been previously demonstrated. The purpose of this study was to test the effectiveness of the individual antioxidant piroctone olamine in two different product forms (shampoo or leave-on product) for activity to improve hair retention. METHODS Female subjects with self-perceived hair thinning participated in an 8-week, double-blind, placebo-controlled, randomized clinical study to evaluate either a piroctone olamine (PO) containing shampoo or a PO containing leave on treatment, each relative to their corresponding placebo formulation Too many periods. Results for phototrichograms, TEWL, and biomarker analysis of scalp condition for the shampoo treatments are discussed. Phototrichogram results are shared for the assessment of the leave on treatment. RESULTS Statistically significant increases in hair amount were observed by phototrichogram after use of both PO-containing products versus placebo formulations. The PO shampoo treatment also significantly decreased oxidative stress on the hair and scalp, and improved scalp condition as assessed by TEWL and scalp biomarker values. CONCLUSION These results illustrate the effectiveness of a cosmetic antioxidant to improve scalp condition thereby improving hair retention. The observed improvements in scalp condition are consistent with previous reports with other antioxidant technologies and suggest that the hair retention effect was achieved by preventing oxidative damage to the scalp.

Objective Increasing hair fullness is a global unmet need for many men and women. An approach to the problem is to decrease hair fall or shedding by reducing scalp stratum corneum oxidation and barrier damage to increase hair retention. This study evaluated a combination of functional antioxidants and barrier-enhancing cosmetic ingredients to improve scalp condition thereby enabling stronger hair anchorage and longer retention. Methods Male and female subjects with normal scalp condition and self-perceived hair thinning participated in a 24-week, double-blind, placebo-controlled, randomized clinical study assessing either a regimen of treatment shampoo and leave-on treatment containing functional antioxidant and barrier-enhancing agents or an identical placebo chassis shampoo control. The functional ingredients were piroctone olamine, zinc pyrithione, zinc carbonate, niacinamide, panthenol, and caffeine. At baseline and after 8, 16, and 24 weeks of product use, several measurements were taken: hair shedding, total hair count (by phototrichogram), hair samples, TEWL, and evaluation of biomarkers of scalp and hair conditions. Subjects also completed self-assessment questionnaires. Results Statistically significant effects for functional ingredient-containing treatment regimen versus a placebo control shampoo formulation were observed for reduced hair shedding, increased total hair count, reduced TEWL, and improvement in scalp biomarker values. Subjects also noticed these improvements assessed via self-assessment questionnaires. Conclusions These results establish that use of functional antioxidant and barrier-enhancing agents to further improve scalp condition can enable a reduction in hair shedding and thus an increase in perceived hair fullness. The underlying improvements in scalp condition suggest the hair benefits were achieved as a result of improved scalp skin barrier and scalp condition leading to a viable preventative approach for hair thinning.

Background: How frequently should the scalp and hair be cleansed? A dearth of objective data has led to confusion both among lay people and experts. Each extreme has potential detrimental effects: overcleaning may lead to surface damage while undercleaning may lead to buildup of harmful stimuli. This situation is complicated because both objective and subjective criteria are relevant to assess optimal cleaning. Objectives: The objective of this work was to combine epidemiological and treatment data with both objective and subjective end points to yield clear data to guide both the consumer and expert as to optimal scalp and hair cleaning practices. Methods: Two studies were conducted with Asian populations without any specific scalp pathologies. An epidemiological study was conducted as a function of natural wash frequency. This was combined with a controlled wash frequency study. In both cases, objective measures of hair and scalp condition were assessed. These were combined with self-assessments of all participants. Results: In the epidemiological study, it was observed that overall satisfaction with hair and scalp condition was achieved when washing 5–6 times per week. This was consistent for both objective and subjective end points. Controlled treatment likewise showed that a daily wash regimen was superior to once per week cleansing for all end points. No objective detrimental effects to hair at this level of cleansing were observed. Conclusions: Two different studies led to the same conclusion: higher wash frequency is both beneficial and more preferred to lower wash frequency among the Asian populations studied. Concerns related to “overcleaning” were unfounded both objectively and subjectively.

In an actively growing scalp hair, the cells proliferating at the basal zone of the hair follicle commence a journey of approximately 4 mm in two weeks before emerging from the scalp surface as a strong rigid fiber. This maturation process of the nascent hair fiber involves many biological, biochemical and biomechanical factors. While we have a rich understanding of the regulatory elements governing biological and biochemical processes, our understanding of the role of biomechanical factors in hair fiber protrusion is virtually null. By adopting a multiscale mechanical modeling approach, here we sought to add a new dimension to the understanding of hair fiber growth. An overall mechanical model constructed to correspond to the entire follicle is complemented and informed by predictions obtained from tissue and cell-scale models. Combined, the simulations suggest that biomechanical features such as follicle geometry, hydrostatic state of tissues layers, material stiffness, keratinization-mediated hardening, and desmosome-correlated shear sliding behaviors are likely to play important roles in hair fiber protrusion. The simulation results predict fine tuning of biomechanical parameters to be a key strategy to ensure smooth hair fiber protrusion while maintaining sufficient anchoring strength against external disturbance. The in silico model of a hair follicle sets a framework for experimental validation and guides the investigation of biomechanical underpinnings of hair growth processes.

The oxidative stress element of unhealthy scalp leads to compromised pre-emergent hair formation and poorly formed hair as it grows. Only cosmetic solutions can minimize the impact of unhealthy hair and to achieve healthy looking and feeling hair, the scalp health must be normalized first. The objectives of this research were to both investigate whether oxidative stress was a relevant aetiological element in scalp dandruff and seborrhoeic dermatitis and whether scalp condition affects the quality of hair that grows from it. Further, this research was designed to determine whether an effective anti-dandruff shampoo would repair and protect the scalp and pre-emergent hair from oxidative stress. This study demonstrated that oxidative stress is an aetiological element relevant to the dandruff condition and that a potentiated ZPT shampoo effectively improves scalp condition, including a reduction in oxidative stress. The compromised hair condition associated with dandruff is concomitantly improved when the scalp condition is improved. It appears that there is a direct link between hair quality and scalp health.

SummaryObjectives To determine whether the oxidative stress transmitted to newly grown hair from an unhealthy scalp has physical consequences to the cuticular condition and function. Methods A uniquely designed 24-week clinical study included 8 weeks of pretreatment with a cosmetic shampoo and 16 weeks of treatment with either a potentiated zinc pyrithione (ZPT) antidandruff shampoo or a placebo cosmetic shampoo. This clinical design allowed the growth and acquisition of hair samples under conditions of varying but known scalp health as a result of treating a dandruff/seborrheic dermatitis (D/SD) population. Two complementary methods were used to characterize the integrity of the cuticular surface. Hair surface hydrophobicity was assessed by quantifying water wetting force using a Wilhelmy balance method. Surface structure and porosity were assessed using dynamic vapor sorption (DVS) to gravimetrically quantify water sorption. Results Chemical oxidative stress to pre-emergent hair has been shown to have negative consequences to hair surface structure. Compared to a placebo shampoo control, use of a potentiated ZPT shampoo improved scalp health and significantly improved the following attributes associated with healthy hair: hair surface hydrophobicity (surface energy) and cuticular moisture barrier effectiveness (dynamic vapor sorption). Conclusions Pre-emergent hair can be negatively impacted by the oxidative stress that occurs with an unhealthy scalp, possibly due to metabolic activity of resident microbes. Manifestations of the oxidative stress include altered cuticle surface properties that are responsible for its protective function; these effects are similar in type to those observed by bleaching post-emergent hair. These alterations have the potential to make the hair, once emerged from the scalp, more susceptible to the cumulative physical and chemical insults responsible for hair feel and look, fiber integrity, and overall retention.

Synopsis Objectives Dandruff is a chronic, relapsing scalp condition that negatively impacts the quality of life of sufferers. Regular use of anti-fungal shampoos represents a proven therapeutic strategy to improve the most common symptoms of flakes and itch. Two recent approaches for enhancing the efficacy of anti-fungal shampoos are maximizing bio-availability of the active material or the addition of a second active material. Our aim is to compare the therapeutic efficacy of these two approaches – maximization of bio-availability of the zinc pyrithione (ZPT) active material or the combination of ZPT with a secondary active material. Methods The anti-fungal potency of shampoos representing each of these approaches was evaluated in vitro using a standard microbiology method. Spatial delivery of ZPT particles in the follicular infundibulum was assessed in vivo using a novel confocal microscopy methodology. Clinical efficacy was assessed in a randomized, double-blind trial involving 620 male and female subjects using scalp flaking and epidermal histamine level as endpoints. Results The shampoo formula with maximized ZPT bio-availability known as the Potentiated ZPT formula exhibited greater anti-fungal potency than the Dual Active shampoo containing both ZPT and climbazole. The Potentiated ZPT formula also delivered more ZPT to the lower infundibulum than the Dual Active shampoo. A 4-week treatment with the Potentiated ZPT formula resulted in superior clinical efficacy compared with the Dual Active product at all 4 weekly time points for both flaking and epidermal histamine endpoints. Conclusion These results highlight the critical role that the shampoo vehicle plays in realizing full potency of active materials. By optimizing the delivery vehicle, the enhanced anti-fungal potency and the maximized spatial delivery of active materials result in greater symptomatic improvement than a product with two active materials. The therapeutic efficacy of a product based on a complex delivery vehicle such as a shampoo must be considered from a full-product perspective rather than just the active system as the non-active components of the composition will often play a significant role in the overall product pharmacology and resultant efficacy. Resume Objectifs Les pellicules representent un etat chronique recurrent du cuir chevelu qui a un impact negatif sur la qualite de vie des personnes atteintes. L'utilisation reguliere de shampooings anti-fongiques offre une strategie therapeutique eprouvee pour ameliorer les symptomes les plus courants de flocons et les demangeaisons. Deux approches recentes pour accroitre l'efficacite de shampooings antifongiques, soit optimisent la bio-disponibilite de la matiere active, soit procedent a l'addition d'une deuxieme matiere active. Notre objectif est de comparer l'efficacite therapeutique de ces deux approches – l'optimisation de la bio-disponibilite du zinc pyrithione (ZPT) actif ou la combinaison du ZPT avec un actif secondaire. Methodes L'activite anti-fongique des shampooings representant chacune de ces approches a ete evaluee in vitro en utilisant une methode standard de microbiologie. La distribution spatiale des particules ZPT dans l'infundibulum folliculaire a ete evaluee in vivo en utilisant une nouvelle methode de microscopie confocale. L'efficacite clinique a ete evaluee dans un essai randomise, en double aveugle impliquant 620 sujets masculins et feminins, a l'aide de la mesure de desquamation du cuir chevelu et du niveau d'histamine epidermique comme criteres. Resultats La formule du shampooing avec ZPT a bio-disponibilite optimisee, nommee ‘ZPT potentialise’ montrait un plus grand pouvoir anti-fongique que le shampooing ‘Actif Double’ contenant a la fois du ZPT et du climbazole. La formule de ‘ZPT potentialise’ a egalement livre plus ZPT a l'infundibulum inferieur que le shampooing ‘Actif Double’. Un traitement de quatre semaines avec la formule de ZPT potentialise a donne lieu a une efficacite clinique superieure a celle du produit aux deux actifs, aux quatre points dans le temps pour les effets d'histamine et de desquamation de l'epiderme. Conclusion Ces resultats soulignent le role crucial que la formule du shampooing joue dans la realisation de la pleine activite des matieres actives. En optimisant le vehicule de deposition, l'activite antifongique amelioree et la distribution spatiale agrandie de l'actif resultent dans une plus notable amelioration des symptomes qu'un produit a deux matieres actives. L'efficacite therapeutique d'un produit base sur une formulation complexe comme un shampooing doit etre consideree dans une perspective du produit entier.

Zinc pyrithione (ZPT) is an antimicrobial material with widespread use in antidandruff shampoos and antifouling paints. Despite decades of commercial use, there is little understanding of its antimicrobial mechanism of action. We used a combination of genome-wide approaches (yeast deletion mutants and microarrays) and traditional methods (gene constructs and atomic emission) to characterize the activity of ZPT against a model yeast, Saccharomyces cerevisiae . ZPT acts through an increase in cellular copper levels that leads to loss of activity of iron-sulfur cluster-containing proteins. ZPT was also found to mediate growth inhibition through an increase in copper in the scalp fungus Malassezia globosa . A model is presented in which pyrithione acts as a copper ionophore, enabling copper to enter cells and distribute across intracellular membranes. This is the first report of a metal-ligand complex that inhibits fungal growth by increasing the cellular level of a different metal.

Summary Background Zinc pyrithione (ZPT) is the active ingredient most commonly used in many antidandruff treatments. Despite decades of successful use to treat human scalps, little is understood about the antifungal mechanism of action of ZPT. Objectives The objective of this study is to understand the molecular mechanism by which ZPT inhibits fungal growth, the underlying basis for its therapeutic activity. Methods Modern systems biology approaches, such as deletion library screening and microarray analysis, were used in combination with traditional measures of metal content, microbial growth and enzyme assays. Results It was shown that ZPT inhibits fungal growth through increased cellular levels of copper, damaging iron–sulphur clusters of proteins essential for fungal metabolism. Conclusions The molecular basis for the antifungal activity of the commonly used active ZPT has been elucidated, more than 50 years since its introduction, as utilizing a copper toxicity mechanism that targets critical iron–sulphur proteins.

Dandruff and seborrhoeic dermatitis are accompanied by bothersome itch. We have established a novel non-invasive methodology to sample histamine levels in the stratum corneum in order to facilitate an understanding of pruritogenesis in this condition. Histamine levels were assessed in two groups of subjects with dandruff before and after 3 weeks of treatment with a commercial potentiated zinc pyrithione shampoo. A comparative population without dandruff was also studied. Itch self-perception was quantified on a visual analogue scale. The histamine level in subjects with dandruff was more than twice that in those who did not have dandruff. Under conditions known to resolve flaking symptoms, the shampoo led to a reduction in histamine in subjects with dandruff to a level that was statistically indistinguishable from those who did not have dandruff. This reduction in histamine was accompanied by a highly significant reduction in the perception of itch intensity. These findings suggest an association between the subjective perception of itch in the scalp and the level of histamine in the skin.

Background Dandruff is a common scalp condition characterized by flakes, pruritus and sometimes mild erythema. These symptoms reflect underlying histopathologic and biochemical events that must be reversed if treatment is to be effective. Objectives This study aimed to better characterize the state of the epidermis in dandruff and to determine how a defined set of skin surface biomarkers of this state change during a successful course of treatment with a potentiated zinc pyrithione (ZPT) shampoo. Methods A population of dandruff sufferers was treated for 3 weeks with a commercial ZPT shampoo or a non-medicated product, and the effect of treatment on adherent scalp flake (ASF) scores was evaluated. Biopsies were taken from lesional sites at baseline and at the end of the study for histomorphometric and histopathologic analysis. Stratum corneum (SC) samples were likewise obtained for evaluation of biochemical markers of inflammation (IL-1α, IL-1RA, IL-8) and barrier integrity (keratin 1, 10, 11; involucrin; SC lipids; human serum albumin). The biomarker profile was evaluated first by comparison with that in non-dandruff subjects at baseline, and then to determine whether any treatment-induced changes were correlated with reductions in flaking in dandruff sufferers. Results Taken together, our studies showed that treatment with the ZPT shampoo led to an improvement in the overall scalp condition as assessed by the resolution of flaking, reduction in epidermal thickness and inflammatory biomarkers, and a dramatic improvement in biomarkers of epidermal barrier integrity. Conclusions The combination of biomarkers examined appears to be a good overall descriptor of the health of the scalp in dandruff, and changes in these biomarkers track with tissue-level events that underlie clinical efficacy in the treatment of dandruff by ZPT shampoo. For the first time, we demonstrate a set of tools that extend beyond flaking scores to provide insight into specific biological changes occurring on the scalp to enable an objective assessment of scalp health.

Summary Background Seborrheic dermatitis and dandruff are common conditions dominated by flakes and itch symptoms. Beyond these observable conditions, the epidermis is highly perturbed and in an inflammation-driven hyperproliferative condition. Aims This review covers current etiologic models and therapeutic strategies. Conclusion Etiology has been controversial in the past due to the search for a singular cause. There are three interrelated factors: Malassezia yeast, sebaceous lipids, and a group of host factors. The yeast and sebaceous lipids interact to yield an inflammatory initiator that leads to hyperproliferation within the epidermis; immature stratum corneum cells are dislodged as large clumps rather than a normal desquamative process. While many therapeutic strategies are theoretically possible, current technology is centered around controlling the Malassezia population. The most convenient and therefore most common format is the shampoo. A wide range of active materials are available; some are more effective than others. Even within a given active, product pharmacology can have a substantial impact on the delivered efficacy, with factors such as amount deposited on the scalp surface and bioavailability of the deposited material being relevant. Beyond choice of active and effective scalp delivery, product usage habits can substantially modulate the efficacy realized by the user.

Scalp skin is physiologically very similar to non-palmoplantar skin of the rest of the body, except for the very high concentration of sebaceous glands (Giacometti, 1965). The scalp environment, however, is much different in being covered by a thick fabric of hair. There are about 250 hair fibers per cm, which results, for a typical individual, in a hair surface area of 50,000 cm relative to the scalp surface area of 600 cm. Together, these parameters indicate the relative inaccessibility of the scalp surface to targeted delivery of actives; relatively low delivery efficiency in this protected environment is an inherent challenge to achieving therapeutic benefits. This is especially true of the most patientfriendly format—shampoos—since a rinsing step is involved and the product cannot interfere with achieving desired hair cosmetic benefits (compliance decreases dramatically if hair cosmetics are poor). This places a large demand on actives with high activity since delivery efficiency will be inherently low as well as development of product pharmacologies that maximize the benefit of the actives employed. This situation will be exemplified for the most common scalp care therapeutic products, those designed to treat dandruff and seborrheic dermatitis (D/SD) utilizing anti-fungal actives to reduce Malassezia content on the scalp. The most common anti-fungal materials used in D/SD scalp therapies include those based on rational chemical design principles (ketoconazole, climbazole, pyrithione zinc (PTZ), piroctone olamine and ciclopirox olamine) as well as materials originating from indeterminate histories (selenium sulfide, sulfur, coal tar, and salicylic acid). Because of the aforementioned demands on activity due to challenging delivery, only those materials with high intrinsic anti-fungal activity should be considered as the basis for therapeutic products. Based on measurement of minimal inhibitory concentrations (MIC) against Malassezia, the most potent materials from this group are pyrithione zinc, selenium sulfide, climbazole, and ketoconazole (VanGerven and Odds, 1995; Schmid and Ruhl-Horster, 1996). For a formulated therapeutic product to be effective, a potent active is a necessary but insufficient condition to achieve activity. The way the active is delivered to the scalp from the product formula, i.e., the product pharmacology, is at least as strong a determinant of in-use activity as the intrinsic active potency. For example, a comparison of clinical flake-reduction efficacy of a variety 1% PTZ-based D/ SD shampoo products demonstrates a wide range of magnitude of therapeutic benefits. Much of this variation is likely due to the varying efficiency of delivery of PTZ, a particulate active, to the scalp surface. Particulate PTZ delivery will be affected by the physical size and shape of the particle (as well as other formulation parameters, which will not be covered further here). Particles which are flat cover the scalp surface more efficiently than those that are not. The particle size is also critical as smaller particles provide better surface coverage but are more difficult to retain on the scalp after rinsing. These two opposing factors result in an optimum size to maximize active delivery. Shampoo product formulations utilizing PTZ particles optimized for delivery outperform those utilizing standard forms of the active (Fig 1). This exemplifies one variable, beyond active potency, that must be considered in selecting a therapeutic treatment. Another important pharmacological variable that must be considered is the role of the ‘‘non-functional’’ excipients in

Despite an increasing knowledge of dandruff and seborrheic dermatitis (D/SD), the pathophysiological understanding is still incomplete but suggests a role of Malassezia yeasts in triggering inflammatory and hyper-proliferative epidermal responses. The objective of this report is to review published literature from in vivo studies of D/SD populations to provide a more complete description of overall scalp health. New biomolecular capabilities establish a depth of pathophysiological understanding not previously achievable with traditional means of investigation. Biomarkers representing inflammation, hyper-proliferation and barrier function are all perturbed by the D/SD condition and robustly respond to therapeutic resolution. These biomarkers can be sampled noninvasively, enabling their use in routine clinical evaluations as either surrogate endpoints or complementary ones to classical signs/symptoms to broaden the etiological learning.

Background Scalp seborrheic dermatitis and dandruff (SD/D) are chronic conditions requiring long-term treatment. There is a common belief that patients frequently experience decreasing benefits over time when using a single product. This physiologic accommodation is termed tachyphylaxis. Aim To systematically investigate the anecdotal belief that tachyphylaxis occurs in long-term treatment of SD/D using quantitative clinical assessments. Methods An international questionnaire completed by 722 dermatologists assessed the belief of tachyphylaxis incidence with pyrithione zinc (PTZ)-based shampoos, time course, occurrence relative to active ingredients, and effect of switching products. Two double-blind, randomized, clinical evaluations were conducted, 24- and 48-week studies, whereby a 1% PTZ shampoo, a 2% PTZ shampoo, or a matched placebo control shampoo was used by each subject for the duration of the study. Dermatologists assessed the adherent scalp flaking (scale of 0–10) at baseline and at specified intervals. Results Sixty-four per cent of responding dermatologists believed tachyphylaxis occurred with PTZ products, and most felt that tachyphylaxis occurred within 3 months of use. Evaluation of mean treatment responses vs. placebo and individual responses as a function of study duration showed a consistent benefit for all products at all time points; therefore, no evidence for tachyphylaxis was found (within 48 weeks of treatment). Conclusion No evidence for tachyphylaxis in SD/D treatment by PTZ-based shampoos was found. Compliance could explain the decreasing response rate seen over time; the solution is to choose an affordable therapeutic product that is effective long term without cosmetic trade-offs.

Application of new molecular and biochemical tools has greatly increased our understanding of the organisms, mechanisms, and treatments of dandruff and seborrheic dermatitis. Dandruff results from at least three etiologic factors: Malassezia fungi, sebaceous secretions, and individual sensitivity. While Malassezia (formerly P. ovale) has long been a suspected cause, implicated by its presence on skin and lipophylic nature, lack of correlation between Malassezia number and the presence and severity of dandruff has remained perplexing. We have previously identified the Malassezia species correlating to dandruff and seborrheic dermatitis. In this report, we show that dandruff is mediated by Malassezia metabolites, specifically irritating free fatty acids released from sebaceous triglycerides. Investigation of the toxic Malassezia free fatty acid metabolites (represented by oleic acid) reveals the component of individual susceptibility. Malassezia metabolism results in increased levels of scalp free fatty acids. Of the three etiologic factors implicated in dandruff, Malassezia, sebaceous triglycerides, and individual susceptibility, Malassezia are the easiest to control. Pyrithione zinc kills Malassezia and all other fungi, and is highly effective against the Malassezia species actually found on scalp. Reduction in fungi reduces free fatty acids, thereby reducing scalp flaking and itch.

Background. Zinc is known to have a critical role in overall human physiology, which likely explains many of its therapeutic uses for the last several thousand years. The specific roles zinc plays in skin health and function are less widely known yet are likely just as critical based on the manifestations of dietary zinc deprivation, which include moderate to severe dermatitis. Objective. To provide a critical review of the scientific literature as to the physiologic importance of zinc to skin, the biochemical basis for these effects, and pharmacologic aspects of zinc therapeutics. Results and Conclusions. Skin is in a continual state of renewal, placing a high demand on zinc-based enzymes and proteins that direct this process. The importance of zinc physiologically is especially evident in studies of wound healing and inflammation reduction. During these processes, the high needs for zinc can be supplemented externally, generally increasing the rates of the natural processes. Topical zinc delivery involves the pharmacologic optimization of zinc delivery, often mediated by the solubility of the zinc material and interactions within the product matrix. DR. SCHWARTZ AND DR. MARSH ARE EMPLOYEES OF PROCTER & GAMBLE, WHICH SUPPORTED THE WORK. PATENT APPLICATIONS FOR TECHNOLOGY DISCUSSED IN THE ARTICLE HAVE BEEN FILED. DR. DRAELOS IS A CONSULTANT TO PROCTER & GAMBLE.

Transmission electron microscopy of scalp tape strips indicates that dandruff scalp possesses abnormal stratum corneum (SC) ultrastructure that is normalized by treatment with small-particle zinc pyrithione (ZPT). Similar abnormalities occur throughout the scalp of those with dandruff, even where no flaking is present. SC abnormalities are consistent with hyperproliferation, including parakeratosis, lipid droplets within corneocytes, few desmosomes, corneocyte membrane interdigitation, and excessive disorganized intercellular lipid. Reversal of SC abnormalities would require treatment of the cause(s) of dandruff, not merely flake removal. A protocol was developed to quantify scalp structural abnormalities by scoring cells from scalp tape strips for yeast number, amount of intercellular lipid, normal intercellular lipid structures, prevalence of intracellular lipid droplets, parakeratotic corneocytes, and corneocyte interdigitation. This protocol was used to compare dandruff and normal SC to dandruff SC treated with either commercial ZPT-containing shampoo or a placebo. Treatment with commercial ZPT shampoo significantly returned SC ultrastructure to normal, suggesting control of the cause of dandruff.

P142 BROAD-SPECTRUM ANTI-FUNGAL ACTIVITY OF PYRITHIONE ZINC AND ITS EFFECT ON THE CAUSES OF DANDRUFF AND ASSOCIATED ITCH Thomas L Dawson, PhD, The Procter and Gamble Company, Cincinnati, OH, United States, Yvonne DeAngelis, BS, The Procter and Gamble Company, Cincinnati, OH, United States, Joseph Kaczsvinsky, PhD, The Procter and Gamble Company, Cincinnati, OH, United States, James Schwartz, PhD, The Procter and Gamble Company, Cincinnati, OH, United States